GENE THERAPY FOR MELANOMA IN HUMANS

详细信息    查看全文

• 作者：Ralf Gutzmer ; MD^a ; DuPont Guerry IV ; MD^b ; ^c
• 刊名：Hematology/Oncology Clinics of North America
• 出版年：1998
• 出版时间：1 June 1998
• 年：1998
• 卷：12
• 期：3
• 页码：519-538
• 全文大小：1197 K

文摘

Malignant melanoma is a promising target for gene therapy: Melanomas are often immunogenic, and salient aspects of their immunobiology are known. Metastatic lesions are often accessible because they are skin-based or in regional lymph nodes. Moreover, disseminated disease usually has a fatal outcome and efficacious treatment is not presently available. Patients at high risk for developing metastasis after resection of the primary tumor can be identified. Therefore, gene therapy may offer adjuvant treatment modalities for such patients in the stage of clinical remission, as well as for patients in advanced stages.

In gene therapy of melanoma, foreign genes are introduced into cells using methods described in detail in other contributions to this issue. The aim is to destroy the tumor (destructive approach) or to revert its malignant phenotype (corrective approach). To achieve the first aim, and based on our current understanding of melanoma immunobiology, genes have been introduced either into melanoma cells or into immune effector cells to evoke or stimulate an immune response against the tumor. Another destructive approach is the introduction of genes into tumor cells that render them sensitive to subsequently delivered drugs by coding for enzymes capable of converting inert prodrugs to active cytotoxics (drug sensitization approach). The corrective gene therapy approach seeks to introduce genes into tumor cells that repair the genetic changes underlying the development and progression of the malignant phenotype and therefore arrest or reverse tumor development. Drug sensitization and corrective gene therapy approaches require targeting gene therapy to tumor cells, as discussed subsequently. Some of these approaches are under investigation in phase I/II clinical studies, as outlined in the final part of this review.